This invention relates to the use of spectrophotometric absorption for non-invasively measuring the chemistry of the blood in the eye.
Photographic retinal oximetry, like pulse oximetry, computes arterial O2 saturation by using variations in the absorption of light in the red and IR (infrared) wavelengths caused by the pulsation of arterial blood. Arterial oxygen saturation of the blood as determined by a photographic retinal oximeter is designated SpO2 (and is shown in FIG. 3). Increased arterial blood flow during systole expands tissue beds by delivering additional blood with each pulse. When a pulse of light is shone onto a blood-perfused tissue bed, each of the arterial pulsations alters the amount of light transmitted through and reflected back from the tissue bed. By working only with the variations in the light caused by the pulsing of the tissue bed, a photographic retinal oximeter can be operated in a fashion to ignore light absorption by nonpulsatile elements in the light transmission pathway (e.g., choroid, retina, lens and cornea). This type of analysis is called transmission (or reflectance) oximetry and it uses light at wavelengths of 660 nm (red light, primarily absorbed by reduced hemoglobin) and 910 or 940 nm (infra-red light, primarily absorbed by oxyhemoglobin).
More recent developments in techniques for non-invasive analysis of patients by using light have enabled the use of reflectance oximetry (as opposed to the transmission oximetry just discussed). This newer technique monitors SpO2 (partial pressure of oxygen in the blood) by measuring light reflected from perfused tissues. This approach could be dangerous for additional monitoring capabilities and comparison with the values obtained by transmission oximetry.
Oximetry describes various spectrophotometric techniques that determine the HbO2 saturation (i.e., saturation of hemoglobin with oxygen). If blood exposed to light of a particular wavelength and intensity, measurement of the light absorbed by the oxygenated hemoglobin moiety (whether partially or fully oxygenated) is proportional to the relative amount of HbO2 present. This relationship can be expressed mathematically by A=alc (Equation 1), where A is the amount of light absorbed, a is the absorption of HbO2 at a given wavelength, 1 is the length of the light path, and c is the concentration of HbO2. Rearranging Equation 1 gives the following mathematic relationship for absorption: a=A/lc (Equation 2). A calibration constant can be derived by comparison of absorption between two substances with identical absorption at a given wavelength (e.g., a standard (st) and an unknown (u) from the equality: (A/lc)st=(A/lc)u (Equation 3). If the light path length is held constant, the concentration of the unknown substance is determined by the relationship: cu=Auxc3x97cst/Ast (Equation 4).
Application of these principles to patient monitoring assumes that the measured change in absorption is a function having as its predominant parameter the different forms of hemoglobin present in the blood. The presence of other substances with spectral activity in the light wavelengths used for analyzing biological fluids and molecules will likely result in erroneous measurements (to some degree). Two applications of these principles are routinely used in the clinical management of anesthetized and critically ill patients.
Pulse oximeteres are dual-wavelength spectrophotometers that use a light-emitting diode as a light source and a photodiode as a light detector. The source and detector are usually incorporated into a digital clip that is applied xe2x80x9cclothes-pinxe2x80x9d fashion to the end of a finger. When the light source and detector are separated by the pulsating arterial vascular bed at the end of the finger, the degree of change in the transmitted light (light emitted minus light absorbed) is proportional to the size of the arterial pulse, the wavelengths of light, and the HbO2 concentration. If the pulse is considered to be entirely due to the passage of arterial blood and the appropriate light wavelengths (e.g., 660 nm and 940 nm) are used, the SpO2 can be continuously measured. The clinical accuracy of pulse oximeters is excellent for HbO2 saturationsxe2x89xa780% when compared with laboratory co-oximeters. At lower oxyhemoglobin concentrations, agreement between the pulse oximeter and the co-oximeter is diminished. Nevertheless, the pulse oximeter still reliably trends the changes in HbO2 saturation.
Fiberoptic techniques allow flow-directed pulmonary artery catheters to measure continuously the HbO2 concentration of mixed venous blood in the pulmonary artery. Mixed venous oximetry is an application of reflectance spectrophotometry, in which light of appropriate wavelengths is flashed down a fiberoptic path; the resultant reflected light from the hemoglobin passes back up the fiberoptic path. The ratio of reflected light between (or among) the different wavelengths is proportional to the mixed venous HbO2 saturation (SvO2). The fiberoptic catheter must be calibrated for reading during use for this technique to provide accurate results. Stability of the calibration is unaffected by temperature variations or by hemoglobin concentration, provided the subject""s hematocrit is at least 40%. Another source of error, calibration curves can shifted by 1% for every 0.1 change in the pH of the subject""s blood. Thus, calibration against (i) a standard sample of known HbO2, (ii) saturation before insertion, or (iii) a measured SvO2 obtained from a blood sample taken after catheter placement, is feasible and reliable (and desirable). Mixed venous fiberoptic oximetry results correlate well with co-oximetric measurement of SvO2. Clinically acceptable accuracy of these techniques is unaffected by body temperature, hemoglobin concentration, cardiac index, or method of calibration.
Noninvasive oximeters typically measure red and infrared light transmitted through and/or reflected by a tissue bed. Accurate estimation of SaO2 (arterial oxygen saturation) using this method encounters several technical problems. First, there are many light absorbers in the path of transmitted light other than arterial hemoglobin (e.g., cornea, lens, and vitreous and venous and capillary blood). The photographic retinal oximeter takes into account the effect of absorption of light by these tissues and venous blood by assuming that only arterial blood pulsates. FIG. 4 illustrates schematically the series of absorbers in a typical sample of living tissue. At the top of FIG. 4 is the xe2x80x9cacxe2x80x9d (pulsatile) component, which represents absorption of light by the pulsating arterial blood in the choroid and retina. The xe2x80x9cdcxe2x80x9d (baseline) component represents absorption of light by the tissue bed, including venous, capillary, and nonpulsatile arterial blood. The pulsatile expansion of the arteriolar bed increases the path length, thereby increases absorbance. Pulse oximeters use only two wavelengths of light:; 660 nm (red light) and 940 nm (near-infrared light). The photographic retinal oximeter first determines the ac component of absorbance at each wavelength and then divides this value by the corresponding dc component to obtain a xe2x80x9cpulse-addedxe2x80x9d absorbance that is independent of the intensity of incident light, both ac and dc values determined photographically at the peak or crest (ac) and trough (dc) of the arterial pulse. The oximeter then calculates the ratio R of these pulse-added absorbance, which is empirically related to SaO2 by the formula R (ac660/dc660) (ac940/dc940) (Eq. 5).
It was a fortuitous coincidence of technology and physiology that allowed the development of solid-state pulse oximeter sensors. Light-emitting diodes are available over a relatively narrow range of the electromagnetic spectrum. Among the available wavelengths are some that not only pass through the skin but also are absorbed by both oxyhemoglobin and reduced hemoglobin. For best sensitivity, the difference between the ratios of the absorbance of HbO2, and Hb at the two wavelengths should be maximized. At a wavelength of 660 nm, reduced hemoglobin absorbs approximately 10 times as much light as does oxyhemoglobin. At the infrared wavelength of 940 nm, the absorption coefficient of oxyhemoglobin (oxygenated hemoglobin) is greater than that of reduced hemoglobin.
Photographic Retinal Oximetry (PRO) could become the standard of care for monitoring chorio-retinal oxygenation just as pulse oximeters do with digital clips during anesthesia. Photographic Retinal Oximetry (PROs) measure pulse rate and oxygen saturation of hemoglobin (SpO2) noninvasively. FIG. 5 displays the oxyhemoglobin dissociation curve that defines the relationship of hemoglobin saturation and oxygen tension. On the steep part of the curve a predictable correlation exists between SaO2 and PO2. In this steep part of the curve, the SaO2 is a good reflection of the extent of hypoxemia and the changing status of arterial oxygenation. Shifts in the oxyhemoglobin dissociation curve to the right or to the left define changes in the affinity of hemoglobin for oxygen. At a PO2, of greater than about 75 mm Hg., the SaO plateaus and loses its ability to reflect changes in PaO2.
Photographic Retinal Oximetry and Pulse Oximetry are based on several premises:
1. The color of blood is a function of oxygen saturation.
2. The change in color results from the optical properties of hemoglobin and its interaction with oxygen.
3. The ratio of oxygenated (O2Hb) and reduced hemoglobin (Hb) can be determined by absorption spectrophotometry.
Photographic Retinal Oximetry combines the technologies of plethysmography and spectrophotometry. Plethysmography produces a pulse trace that is helpful in tracking circulation. Oxygen saturation can be determined spectrophotometrically based upon the Beer-Lambert law: at a constant flash intensity and hemoglobin concentration, the intensity of light transmitted through the transparent ocular media (cornea, lens vitreous) and the retina and choroid of the mammalian eye is a logarithmic function of the oxygen saturation of hemoglobin. Two wavelengths of light are required to distinguish O2Hb from reduced Hb. Light-emitting diodes in the pulse sensor emit red (660 nm) and near infrared (940 nm) light. The percentage of each of O2Hb and reduced Hb is determined by measuring the ratio of infrared and red light sensed by a photodetector. Pulse oximeters perform a plethysmographic analysis to differentiate the pulsatile xe2x80x9carterialxe2x80x9d Hb saturation from the nonpulsatile signal resulting from absorption by xe2x80x9cvenousxe2x80x9d blood and by other tissues such as skin, muscle, and bone. The absence of a pulsatile waveform during extreme hypothermia or hypoperfusion limits the ability of a photographic retinal oximeter to calculate the SpO2 under these conditions.
The SpO2, measured by photographic retinal oximetry is not the same as the arterial saturation (SaO2) measured by a laboratory co-oximeter. Photographic retinal oximetry measures the xe2x80x9cfunctionalxe2x80x9d saturation, which is defined by the equation: Functional SaO2=[O2Hb÷(O2Hb+reduced Hb)]xc3x97100. Laboratory co-oximeters use multiple wavelengths to distinguish other types of Hb by their characteristic absorption. Co-oximeters measure the xe2x80x9cfractionalxe2x80x9d saturation which is defined by the following equation: Fractional SaO2=[O2Hb/(O2Hb+reduced Hb+COHb+MetHb)]xc3x97100 (Equation 6). In clinical circumstances where other Hb moieties are present, the SpO2 measurement is higher than the SaO2 reported by the blood gas laboratory. In most patients, MetHb and COHB are present in low concentrations so that the xe2x80x9cfunctionalxe2x80x9d saturation approximates the xe2x80x9cfractionalxe2x80x9d value.
Pulse oximetry has been utilized in all patient age groups to detect and prevent hypoxemia. The clinical benefits of pulse oximetry are enhanced by its simplicity. Modern pulse oximeters are noninvasive, continuous, and auto-calibrating. They have quick response times and their battery backup provide monitoring during transport. The clinical accuracy is typically reported to be xc2x12-3% at 70-100% saturation and xc2x13% at 50-70% saturation. Published data from numerous investigations support accuracy and precision reported by instruments manufacturers. Photographic retinal oximeters should also have similar accuracy and precision, be non-invasive and auto-calibrating.
The appropriateness of a decision to use a particular monitoring technique, pulse oximetry versus photographic retinal oximetry, necessitates an appreciation of both physiologic and technical limitations. Despite the numerous clinical benefits of pulse oximetry, other factors impact on its accuracy and reliability. Factors that are deleterious to pulse oximetry measurements include: whether the patient is anesthetized; the presence of such compounds as dyshemoglobins, vital dyes, and/or nail polish; variations and type of ambient light; LED variability (including variability due to manufacture, power supply, and so on); motion artifact; and background xe2x80x9cnoisexe2x80x9d. Electrocautery can interfere with pulse oximetry if the radio-frequency emissions are sensed by the photodetector. Reports of burns and/or pressure necrosis at the oximeter situs exist but are infrequent. These complications can be reduced by inspecting the digits during monitoring. None of these problems exist or interfere with photographic retinal oximetry.
There is overwhelming evidence supporting the capability of photographic retinal oximetry for detecting desaturation before it is clinically apparent. Photographic retinal oximetry has a wide applicability in many hospital and non-hospital settings. Some sources of error that could be apparent with photographic retinal oximetry are those that exist with pulse oximetry. A source of photographic retinal oximetry error that deserves mention is the interference caused by dyes and abnormal hemoglobins. Methylene blue, indocyanine green, and indigo carmine cause transient, apparent desaturation when administered intravenously. Methylene blue has the most profound and complex effects on SPO2. It both produces and clears methemoglobin, causes a transient increase in cardiac output followed by cardiac depression, and has an absorbance peak at 668 nm that interferes with the oximeter""s detection of red absorbance and indicates desaturation.
Methemoglobin can cause falsely high or low SPO2 readings, depending on the relative amounts of oxyhemoglobin and reduced hemoglobin. However, as the methemoglobin level increases, the SPO2 decreases to 80-85% and then remains constant.
Carboxyhemoglobin is read as approximately 90% saturated by photographic retinal oximeters. Therefore, it can cause falsely elevated SpO2 readings in heavy smokers or in those with carbon monoxide poisoning if they have xe2x80x9ctruexe2x80x9d low SaO2 levels with elevated carboxyhemoglobin levels. Fetal hemoglobin has no clinically significant effect on photographic retinal oximetry.
These and other features and advantages of the invention will be more fully understood from the following description of specific embodiments of the invention taken together with the accompanying drawings.